Fischer Ellen Kure, Drago Antonio
Department of Clinical Medicine, Aarhus University-Psykiatrisk Forskningsenhed Vest, GI Landevej 49, 1, 7400, Herning, Denmark.
J Neural Transm (Vienna). 2017 Jul;124(7):765-774. doi: 10.1007/s00702-017-1730-y. Epub 2017 May 5.
Cognitive processes have a genetic component and are impaired in Schizophrenia (SKZ). The exact nature of such impairment escapes definition. The aim of the present contribution was the identification of the molecular pathways enriched with mutations (SNPs) associated with cognitive performance during antipsychotic treatment. 765 individuals from the CATIE study, males = 559, mean age 40.93 ± 11.03 were included. Working memory and the verbal memory were the evaluated outcomes. A mixed regression model for repeated measures served in R for clinical and molecular pathway analysis. The analysis of quality was conducted under the following criteria: minor allele frequency >0.01, genotype call rate >95%, missing data frequency <5%, Hardy-Weimberg equilibrium threshold >0.0001. The inflation factor was controlled by lambda values. Input for the pathway analysis was SNPs at a p level <0.05 of association genome-wide. Gender, age, education and the duration of the disease were the clinical and socio-demographic variables associated with the cognitive performance. 4268977 SNPs were available after imputation and quality analysis. Pathways related to inflammation and oxidation were the most strongly associated with verbal memory and working memory at a conservative adjusted p value < 0.01. We report that inflammation and in particular the pathway associated with arachidonic acid was enriched in mutations associated with poorer performance at the verbal memory and working memory tasks in SKZ patients.
认知过程具有遗传成分，且在精神分裂症（SKZ）中会受损。这种损伤的确切性质难以定义。本研究的目的是确定在抗精神病药物治疗期间与认知表现相关的富含突变（单核苷酸多态性，SNPs）的分子途径。纳入了来自CATIE研究的765名个体，男性 = 559名，平均年龄40.93 ± 11.03岁。工作记忆和言语记忆是评估的结果。在R语言中使用重复测量的混合回归模型进行临床和分子途径分析。根据以下标准进行质量分析：次要等位基因频率>0.01，基因型检出率>95%，缺失数据频率<5%，哈迪-温伯格平衡阈值>0.0001。通过lambda值控制膨胀因子。途径分析的输入是全基因组关联p值<0.05的SNPs。性别、年龄、教育程度和疾病持续时间是与认知表现相关的临床和社会人口统计学变量。经过插补和质量分析后，有4268977个SNPs可用。在保守调整后的p值<0.01时，与炎症和氧化相关的途径与言语记忆和工作记忆的相关性最强。我们报告，在SKZ患者中，炎症，特别是与花生四烯酸相关的途径，在与言语记忆和工作记忆任务表现较差相关的突变中富集。
